practice of echocardiography in infective endocarditis

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RECOMMENDATIONS Recommendations for the practice of echocardiography in infective endocarditis Gilbert Habib (France) * , Luigi Badano (Italy), Christophe Tribouilloy (France), Isidre Vilacosta (Spain), and Jose Luis Zamorano (Spain) Scientific Committee: Maurizio Galderisi (Italy), Jens-Uwe Voigt (Belgium), Rosa Sicari (Italy) Document Reviewers: Bernard Cosyns (Belgium), Kevin Fox (UK), Svend Aakhus (Norway) On behalf of the European Association of Echocardiography Service de Cardiologie, CHU La Timone, Bd Jean Moulin, 13005 Marseille, France Received 20 December 2009; accepted after revision 30 December 2009 Echocardiography plays a key role in the assessment of infective endocarditis (IE). It is useful for the diagnosis of endocarditis, the assessment of the severity of the disease, the prediction of short- and long-term prognosis, the prediction of embolic events, and the follow-up of patients under specific antibiotic therapy. Echocardiography is also useful for the diagnosis and management of the complications of IE, helping the physician in decision-making, particularly when a surgical therapy is considered. Finally, intraoperative echocardiography must be performed in IE to help the surgeon in the assessment and management of patients with IE during surgery. The current ‘recommendations for the practice of echocardiography in infective endocarditis’ aims to provide both an updated summary concerning the value and limitations of echocardiography in IE, and clear and simple recommendations for the optimal use of both transthoracic and transoesophageal echocardiography in IE. ----------------------------------------------------------------------------------------------------------------------------------------------------------- Keywords Echocardiography Endocarditis Valve disease Table of Contents Introduction .................................. 202 Chapter 1: Echocardiography for the diagnosis of infective endocarditis ........................... 203 1. When to perform echocardiography in infective endocarditis? .............................. 203 2. Transthoracic or transoesophageal echocardiography in suspected infective endocarditis? ................. 203 3. Anatomical features ......................... 203 4. Echocardiographic criteria ..................... 204 5. Limitations and pitfalls of echocardiography for the diagnosis of infective endocarditis ................ 205 Chapter 2: Echocardiography for the diagnosis and management of complications of infective endocarditis ........ 207 1. Heart failure/haemodynamic indications ............ 207 2. Perivalvular extension/infectious indications ......... 208 3. Embolic events/embolic indications ............... 210 4. Other complications......................... 211 Chapter 3: Echocardiography for the follow-up and prognostic assessment of IE ........................ 211 1. Prognostic assessment at admission ............... 211 2. Echocardiographic follow-up under therapy ......... 212 3. Follow-up after discharge and long-term prognosis..... 212 Chapter 4: Intraoperative echocardiography.............. 212 Chapter 5: Echocardiography in specific clinical conditions .... 213 1. Prosthetic valve infective endocarditis ............. 213 2. Cardiac device-related infective endocarditis ......... 214 3. Right heart infective endocarditis ................ 215 4. Negative blood culture infective endocarditis ........ 217 Conclusion and future directions ..................... 217 Introduction Infective endocarditis (IE) is a life-threatening disease still associ- ated with a high mortality rate. 1,2 Several complications may occur during the course of IE, including embolic events, perivalvu- lar extension, and valvular destruction causing heart failure. These main complications are the cause of the persistent high morbidity and mortality of the disease. 3 They are also the main reasons for * Corresponding author. Tel: þ33 4 91 38 63 79, Email: [email protected] Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2010. For permissions please email: [email protected]. European Journal of Echocardiography (2010) 11, 202–219 doi:10.1093/ejechocard/jeq004

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Page 1: Practice of echocardiography in infective endocarditis

RECOMMENDATIONS

Recommendations for the practice ofechocardiography in infective endocarditisGilbert Habib (France)*, Luigi Badano (Italy), Christophe Tribouilloy (France),Isidre Vilacosta (Spain), and Jose Luis Zamorano (Spain)

Scientific Committee: Maurizio Galderisi (Italy), Jens-Uwe Voigt (Belgium),Rosa Sicari (Italy)Document Reviewers: Bernard Cosyns (Belgium), Kevin Fox (UK), Svend Aakhus(Norway)On behalf of the European Association of EchocardiographyService de Cardiologie, CHU La Timone, Bd Jean Moulin, 13005 Marseille, France

Received 20 December 2009; accepted after revision 30 December 2009

Echocardiography plays a key role in the assessment of infective endocarditis (IE). It is useful for the diagnosis of endocarditis, the assessment ofthe severity of the disease, the prediction of short- and long-term prognosis, the prediction of embolic events, and the follow-up of patientsunder specific antibiotic therapy. Echocardiography is also useful for the diagnosis and management of the complications of IE, helping thephysician in decision-making, particularly when a surgical therapy is considered. Finally, intraoperative echocardiography must be performedin IE to help the surgeon in the assessment and management of patients with IE during surgery. The current ‘recommendations for the practiceof echocardiography in infective endocarditis’ aims to provide both an updated summary concerning the value and limitations of echocardiography inIE, and clear and simple recommendations for the optimal use of both transthoracic and transoesophageal echocardiography in IE.- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -Keywords Echocardiography † Endocarditis † Valve disease

Table of ContentsIntroduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 202Chapter 1: Echocardiography for the diagnosis of infective

endocarditis . . . . . . . . . . . . . . . . . . . . . . . . . . . 2031. When to perform echocardiography in infective

endocarditis? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2032. Transthoracic or transoesophageal echocardiography in

suspected infective endocarditis?. . . . . . . . . . . . . . . . . 2033. Anatomical features . . . . . . . . . . . . . . . . . . . . . . . . . 2034. Echocardiographic criteria . . . . . . . . . . . . . . . . . . . . . 2045. Limitations and pitfalls of echocardiography for the

diagnosis of infective endocarditis . . . . . . . . . . . . . . . . 205Chapter 2: Echocardiography for the diagnosis and management

of complications of infective endocarditis . . . . . . . . 2071. Heart failure/haemodynamic indications . . . . . . . . . . . . 2072. Perivalvular extension/infectious indications . . . . . . . . . 2083. Embolic events/embolic indications . . . . . . . . . . . . . . . 2104. Other complications. . . . . . . . . . . . . . . . . . . . . . . . . 211

Chapter 3: Echocardiography for the follow-up and prognosticassessment of IE . . . . . . . . . . . . . . . . . . . . . . . . 211

1. Prognostic assessment at admission. . . . . . . . . . . . . . . 211

2. Echocardiographic follow-up under therapy . . . . . . . . . 2123. Follow-up after discharge and long-term prognosis. . . . . 212

Chapter 4: Intraoperative echocardiography. . . . . . . . . . . . . . 212Chapter 5: Echocardiography in specific clinical conditions . . . . 213

1. Prosthetic valve infective endocarditis . . . . . . . . . . . . . 2132. Cardiac device-related infective endocarditis . . . . . . . . . 2143. Right heart infective endocarditis . . . . . . . . . . . . . . . . 2154. Negative blood culture infective endocarditis . . . . . . . . 217

Conclusion and future directions . . . . . . . . . . . . . . . . . . . . . 217

IntroductionInfective endocarditis (IE) is a life-threatening disease still associ-ated with a high mortality rate.1,2 Several complications mayoccur during the course of IE, including embolic events, perivalvu-lar extension, and valvular destruction causing heart failure. Thesemain complications are the cause of the persistent high morbidityand mortality of the disease.3 They are also the main reasons for

* Corresponding author. Tel: þ33 4 91 38 63 79, Email: [email protected]

Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2010. For permissions please email: [email protected].

European Journal of Echocardiography (2010) 11, 202–219doi:10.1093/ejechocard/jeq004

Page 2: Practice of echocardiography in infective endocarditis

surgery, which is performed during the active phase of the disease(early surgery) in about half of patients with acute IE.4

Echocardiography has a known key role in the diagnosis of IEand the prediction of embolic risk. Moreover, echocardiographyis also crucial for the prognostic assessment of patients with IE,for their follow-up under therapy, and during the peroperativeperiod.5

Several guidelines have been proposed in the past few yearsconcerning the prevention, diagnosis, and treatment of IE.6 –10 Ineach of them, the value of echocardiography was clearly outlined.However, all previous recommendations suffer from severallimitations. First, the respective indications of transthoracic (TTE)and transoesophageal (TEE) echocardiography, and the value ofechocardiography in predicting embolic events, have been thesource of conflicting publications and recommendations. Secondly,no previous recommendation has specifically addressed the role ofechocardiography in IE.

The current ‘recommendations for the practice of echocardiographyin infective endocarditis’ aims to provide both an updated summaryconcerning the value and limitations of echocardiography in IE,and clear and simple recommendations for the optimal use ofboth TTE and TEE in IE, assisting health care providers in clinicaldecision-making. These recommendations were obtained byexpert consensus after thorough review of the literature available.

Chapter 1: Echocardiographyfor the diagnosis of infectiveendocarditis

1. When to perform echocardiographyin infective endocarditis?Infective endocarditis may be suspected in a variety of very differ-ent initial clinical situations,10 including heart failure, cerebralembolism, pacemaker (PM) infection, or isolated fever. Other situ-ations requiring echocardiographic examination include feverassociated with a regurgitant heart murmur, known cardiacdisease, bacteraemia, new conduction disturbance, and embolicevents of unknown origin.10 Finally, IE may be suspected both invery acute situations including cardiogenic or septic shock and inmore insidious presentations. To avoid overuse of echocardiogra-phy, the decision to perform or not an echocardiographic examin-ation must take into account the pre-test probability of the disease.Echocardiography should be performed in the clinical situations inwhich IE is suspected, as described in the ESC guidelines.10

However, whatever the level of suspicion, the most importantissue is that, in all these situations, echocardiography must be per-formed as soon as possible in order to confirm or rule out thediagnosis of IE at the earliest opportunity.

2. Transthoracic or transoesophagealechocardiography in suspected infectiveendocarditis?Figure 1 is an algorithm proposed by the recent Task Force on thePrevention, Diagnosis, and Treatment of Infective Endocarditis ofthe European Society of Cardiology,10 illustrating the respective

indications of TTE and TEE. Transthoracic echocardiography mustbe performed first in all cases, because it is a non-invasive techniquethat provides useful information for both the diagnosis and theassessment of IE severity. Transesophageal echocardiography mustalso be performed in the majority of patients with suspected IE,because of its better image quality and better sensitivity, particularlyfor the diagnosis of perivalvular involvement. The only situation inwhich TTE may be considered sufficient is the case of good-qualitynegative TTE associated with a low level of clinical suspicion.

3. Anatomical featuresKnowledge of the anatomical features of IE is fundamental in orderto better understand, analyse, and describe the echocardiographicfindings (Table 1). Anatomically, IE is characterized by a combi-nation of vegetations, destructive lesions, and abscess formation.

3.1. Vegetations are typically attached on the low-pressure side ofthe valve structure, but may be located anywhere on the com-ponents of the valvular and subvalvular apparatus, as well ason the mural endocardium of the cardiac chambers or theascending aorta. When large and mobile, vegetations areprone to embolism and less frequently to valve or prostheticobstruction.

3.2. Destructive valve lesions are very frequently associated withvegetations or may be observed alone. They may provokevalve aneurysm, perforation or prolapse, and chordae orless frequently papillary muscle rupture. The usual final conse-quences of these lesions are severe valve regurgitation andheart failure.

3.3. The third main anatomical feature of IE is abscess formation.Abscesses are more frequent in aortic and prostheticvalve IE and may be complicated by pseudoaneurysm orfistulization.

These three anatomical features are frequently present togetherand must be meticulously described by the echocardiographicexamination (Table 1).

Figure 1 Algorithm showing the role of echocardiography inthe diagnosis and assessment of infective endocarditis (adaptedfrom Habib et al.10 with permission). IE, infective endocarditis;TTE, transthoracic echocardiography; TEE, transoesophagealechocardiography.

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4. Echocardiographic criteriaIn 1994, Durack proposed a new classification of IE (Duke criteria),11

including, for the first time, echocardiography as a major criterion forIE. The major echographic criteria for IE are vegetation, abscess, andnew dehiscence of a prosthetic valve (Figure 2).

4.1. VegetationThe vegetation is the hallmark lesion of IE. Typically, vegetationpresents as an oscillating mass attached to a valvular structure,with a motion independent to that of the valve (Figures 2A and3). However, vegetations may also present as non-oscillatingmasses with atypical location (Figure 4A). The sensitivity of TTEfor the diagnosis of vegetations is about 75%, but it may bereduced in case of low echogenicity, very small vegetations, andin IE affecting intracardiac devices or prostheses. Transoesophagealechocardiography enhances the sensitivity of TTE to about 85–

90% for the diagnosis of vegetations, while more than 90% speci-ficity has been reported for both TTE and TEE.12

4.2. Abscess and perivalvular involvementThe second major echocardiographic criterion for endocarditis isthe presence of a perivalvular abscess. Abscesses are more fre-quently observed in aortic valve IE and usually involve themitral-aortic intervalvular fibrosa.13 They are also more frequentin prosthetic valve IE. Abscess typically presents as a perivalvularzone of reduced echo density, without colour flow detectedinside. The diagnosis is easy in the presence of a clear free-spacein the aortic root (Figure 2B), but may be much more difficult atthe early stage of the disease when only a thickening of the aorticroot is observed (Figure 4B). The sensitivity of TTE for the diagnosisof abscesses is about 50%, compared with 90% for TEE. Specificityhigher than 90% has been reported, for both TTE and for TEE.14

Therefore, TEE needs to be performed in all cases of aortic valveIE and as soon as an abscess is suspected.14 However, small anteriorabscesses are sometimes difficult to diagnose by TEE, and may bebetter evaluated by TTE. Consequently, both TTE and TEE aremandatory in suspected perivalvular involvement.

Other perivalvular complications include pseudoaneurysm andfistulization, which may both complicate the abscess formation.Pseudoaneurysm is characterized anatomically by a perivalvularcavity communicating with the cardiovascular lumen. The typicalechographic appearance is that of a pulsatile perivalvular echo free-space with colour Doppler flow inside. Formation of a fistula maybe a complication of both abscesses and pseudoaneurysm. It is ana-tomically defined by a communication between two neighbouringcavities and echographically by a colour Doppler communicationbetween two adjacent cavities.

4.3. New dehiscence of a prosthetic valveDehiscence of a prosthetic valve represents the third main diag-nostic criterion for IE.11 Infective endocarditis must be suspectedin the presence of new perivalvular regurgitation, even in theabsence of a vegetation or abscess (Figure 2C). Transoesophagealechocardiography has a better sensitivity than TTE for this diagno-sis, especially in mitral prosthetic valve IE.

4.4. Other echocardiographic findings in infectiveendocarditisOther echocardiographic features are not main criteria for IE, butmay be suggestive of the diagnosis. They include valve destructionand prolapse, aneurysm and/or perforation of a valve. The most fre-quent is anterior mitral valve leaflet perforation which is usually acomplication of aortic valve IE. It may be observed either isolatedor as a complication of a mitral valve aneurysm. Perforation of themitral valve may be the consequence of a regurgitant jet throughan infected aortic valve and is best visualized by TEE.15

In addition, both TTE and TEE are useful for the assessment ofthe underlying valve disease, and for the evaluation of conse-quences of IE, including:

† left ventricular size and function† quantification of valve regurgitation/obstruction† right ventricular function, estimation of pulmonary pressures† presence and quantification of a pericardial effusion.

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Table 1 Anatomic and echocardiographic definitions(adapted from Habib et al.10 with permission)

Surgery/necropsy Echocardiography

Vegetation Infected massattached to anendocardialstructure, or onimplantedintracardiacmaterial

Oscillating ornon-oscillatingintracardiac mass onvalve or otherendocardialstructures, or onimplantedintracardiac material

Abscess Perivalvular cavitywith necrosis andpurulent materialnotcommunicatingwith thecardiovascularlumen

Thickened,non-homogeneousperivalvular area withechodense orecholucentappearance

Pseudoaneurysm Perivalvular cavitycommunicatingwith thecardiovascularlumen

Pulsatile perivalvularecho-free space, withcolour-Doppler flowdetected

Perforation Interruption ofendocardial tissuecontinuity

Interruption ofendocardial tissuecontinuity traversedby colour-Dopplerflow

Fistula Communicationbetween twoneighbouringcavities through aperforation

Colour-Dopplercommunicationbetween twoneighbouring cavitiesthrough a perforation

Valve aneurysm Saccular outpouchingof valvular tissue

Saccular bulging ofvalvular tissue

Dehiscence of aprostheticvalve

Dehiscence of theprosthesis

Paravalvularregurgitationidentified by TTE/TEE, with or withoutrocking motion of theprosthesis

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5. Limitations and pitfalls ofechocardiography for the diagnosisof infective endocarditisAlthough echocardiography plays a major role in the diagnosis of IEand gives a definite diagnosis of IE in a majority of patients, atypicalor doubtful results are not rare, particularly at the early stage ofthe disease, and in patients with intracardiac materials (see Chapter 5).

The clinician must be aware that:

(i) both the sensitivity and specificity of TTE and TEE are not 100%;(ii) a negative echocardiographic examination does not rule out IE;(iii) repeat TTE/TEE may be necessary in some situations;(iv) results of the echographic study must be interpreted with

caution, taking into account the clinical presentation and thelikelihood of IE.

Figure 2 The three main echocardiographic criteria for endocarditis (TEE). (A) Large vegetation on the anterior mitral leaflet with chordaerupture (arrow). (B) Abscess: zone of reduced density (arrow) on the posterior part of the aortic root. (C) New prosthetic regurgitation(arrow) affecting a mechanical mitral prosthetic valve. LA, left atrium; LV, left ventricle; RV, right ventricle; Ao, aorta; A, abscess.

Figure 3 Echocardiographic/anatomical correlations. (A) TEE: long vegetation on the anterior mitral leaflet (arrow). (B) Anatomical corre-lation: large vegetation (arrow). LA, left atrium; LV, left ventricle; MV, mitral valve.

Echocardiography in infective endocarditis 205

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1. Echocardiography is not 100% sensitive for thediagnosis of infective endocarditisA negative echocardiogram may be observed in about 15% of IE.The most frequent explanations for a negative echocardiogramare very small vegetations and difficulties in identifyingvegetations in the presence of pre-existent severe lesions (mitralvalve prolapse, degenerative lesions, and prosthetic valves).16 Simi-larly, the diagnosis of IE may be more difficult when vegetations arenon-oscillating and/or atypically located. In addition, the diagnosismay be difficult at the early stage of the disease, when vegetationsare not yet present or too small to be identified.17 In one series18

of 105 patients with suspected IE, 65 cases had initial negative TEEand in 3 cases, vegetations appeared on a subsequent examination.For this reason,10 a normal echocardiogram does not completelyrule out IE, even if TEE is performed and even in expert hands.A repeat examination has to be performed 7–10 days after thefirst examination in case of high level of clinical suspicion oreven earlier when justified by the clinical presentation, forexample in suspected postoperative staphylococcal prostheticvalve endocarditis (PVE). The additional diagnostic value of athird examination is very low.19

Similarly, the diagnosis of a perivalvular abscess may be difficult,even with the use of TEE, in case of small abscesses, when echo-cardiography is performed very early in the course of thedisease, during the immediate postoperative period, or when theechogenicity is reduced by a prosthetic valve or severe valvularor perivalvular calcifications. Diagnosis of an abscess may be

particularly difficult in patients with abscess localized aroundcalcification areas in the posterior mitral annulus.20 Three-dimensional echocardiography may be useful in some situations(abscesses, mitral valve perforation), but brings little additionalinformation when compared with conventional two-dimensionalechocardiography.21

2. Echocardiography is not 100% specific for the diagnosisof infective endocarditisConversely, false diagnosis of IE may occur in several situations; forexample, it may be difficult to differentiate between vegetations andthrombi, prolapsed cusp, cardiac tumours, myxomatous changes,Lambl’s excrescences, strands, or non-infective vegetations (maranticendocarditis).16 Non-infective vegetations are impossible to differen-tiate from infective vegetations. They can be suspected in the presenceof small and multiple vegetations, changing from one examination toanother, and without associated abscess or valve destruction.

Key pointsBoth TTE and TEE are mandatory in the majority ofpatients with suspected or definite IE. The sensitivity andspecificity of echocardiography are reduced in some sub-groups, including PVE and patients with intracardiacdevices. Echocardiography must be performed early, assoon as the diagnosis of IE is suspected and must berepeated in case of persisting high level of clinical

Figure 4 Difficult echocardiographic cases. (A) Left panel: small vegetation on the interventricular septum (arrow) in a patient with IE com-plicating a hypertrophic obstructive cardiomyopathy. Right panel: disappearance of the vegetation after antibiotic therapy. (B) Isolated thickeningof the posterior part of the aortic root in a patient with a bioprosthetic aortic valve IE. LA, left atrium; LV, left ventricle; Ao, aorta.

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suspicion. All echographic results must be interpretedtaking into account the clinical presentation of the patient.

Recommendations10

(i) TTEis recommendedasthefirst-line imagingmodality insuspected IE;

(ii) TEE is recommended in patients with high clinical suspi-cion of IE and a normal TTE;

(iii) TEEshouldbeconsidered in themajorityofadultpatientswith suspected IE, even in cases with positive TTE;

(iv) Repeat TTE/TEE within 7–10 days is recommended incase of initially negative examination when clinical suspi-cion of IE remains high;

(v) TEE is not indicated in patients with a good-quality nega-tive TTE and low clinical suspicion of IE.

Chapter 2: Echocardiography forthe diagnosis and managementof complications of infectiveendocarditisHeart failure, perivalvular extension, and embolic events representthe three most frequent and severe complications of IE. They arealso the three main indications for early surgery (i.e. while thepatient is still receiving antibiotic treatment), which is performedin almost 50% of cases.4,10,22 Echocardiography, clearly the refer-ence method for the diagnosis of vegetation, abscess, new regurgi-tation, or new prosthetic valve dehiscence, plays a key role in thediagnosis and management of these complications.

Echocardiography helps clinicians not only for taking thedecision to operate or not, but also for choosing the optimaltiming of surgery. The recent Task Force on the Prevention, Diag-nosis, and Treatment of Infective Endocarditis of the EuropeanSociety of Cardiology introduced this notion of timing of surgeryand separated patients operated on as an emergency (within24 h) or urgent (within a few days) basis, or later, after at least 1or 2 weeks of antibiotic therapy10 (Table 2).

1. Heart failure/haemodynamicindicationsHeart failure (HF) represents the most frequent (40–60% of cases)indication for surgery in IE.4 Recent European guidelines rec-ommend early surgery to be performed in patients with acuteregurgitation and HF, as well as in patients with obstructive veg-etations.10 Echocardiography is useful in both situations.

Valve destruction causing acute regurgitation is the most charac-teristic lesion leading to HF in native valve IE.10,23,24 Echocardiogra-phy is mandatory as soon as symptoms or signs of HF occur, inorder to determine the cause of HF and the haemodynamic toler-ance. Rapid diagnosis and assessment of severity is fundamental,considering the high mortality risk of severe acute regurgitationunresponsive to medication without surgical treatment. A normal(or only slightly increased) left ventricular size and ejection fractionin the presence of severe aortic or mitral regurgitation is typical foracute regurgitation.23–25 However, in patients with history of

chronic regurgitation, the left ventricle may be enlarged. Two-dimensional echocardiography combined with pulsed, continuous,and colour Doppler enable (i) a detailed assessment of themechanism (valve perforation, cusp fenestration, torn leaflet, flailmitral leaflet due to ruptured infected chordae, or interferenceof the vegetation mass with leaflet closure) and (ii) a reliablequantification and evaluation of the haemodynamic tolerance of

Table 2 Indications and timing of surgery in left-sidednative valve infective endocarditis (adapted from Habibet al.10 with permission)

Emergency surgery: surgery performed within 24 h; urgent surgery: within a fewdays; elective surgery: after at least 1 or 2 weeks of antibiotic therapy.aClass of recommendation.bLevel of evidence.cSurgery may be preferred if procedure preserving the native valve is feasible.

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the regurgitation (cardiac output, left and right ventricular fillingpressures, pulmonary arterial pressure, left and right ventricularfunction).10,24 Some echocardiographic findings, such as extensivedestructive valve lesions, massive regurgitation, or associatedabscess or pseudoaneurysm, suggest the need for early surgery(Figure 5). Due to rapid elevation of the left ventricular end-diastolic pressures, premature mitral valve closure associatedwith short pressure half-time of the aortic regurgitant flow(,200 ms) and restrictive mitral inflow may be observed inacute severe aortic regurgitation,5,10,24,27,28 also suggesting theneed for surgery. In aortic IE with aortic regurgitation, a secondaryinfection of the ventricular surface of the anterior mitral leafletmay occur ( jet lesion), resulting in the formation of an aneurysmthat may lead to the perforation of the anterior mitral leaflet(Figure 6) and to consequent mild-to-severe acute mitral regurgita-tion.25,26,29 Mitral valve aneurysms appear on two-dimensionalechocardiography as a bulge of the anterior leaflet protrudinginto the left atrium (Figure 7). Transthoracic echocardiographyand TEE are the procedures of choice for diagnosis of mitralvalve aneurysm and perforation. Careful echocardiographic exam-ination of the mitral leaflets is required in all patients with aortic IE,because small aneurysms or perforations may be easily missed.

Less frequently, HF may be due to obstructive vegetationsresulting in functional valve stenosis or due to intra-cardiacshunts generally associated with major destructive lesions.10 In

cases with obstructive vegetations resulting in HF, two-dimensionalechocardiography visualizes the mass that partially obstructs thevalve orifice. Elevated transvalvular gradients and reduced orificearea can be measured with Doppler echocardiography.

Finally, HF may be due to myocarditis or myocardial infarction.Echocardiography allows the evaluation of global and regional leftand right ventricular function and identifies these complications.

When surgery has not been performed on an urgent basis, patientmust be closely followed-up by repeated echocardiographic exam-inations in order to detect new worsening of cardiac lesions.

Key pointsHeart failure is the most frequent and severe complicationof IE. Urgent TTE is required as soon as symptoms orsigns of HF are detected. It has a primary role in determin-ing the cause of HF and in the evaluation of the haemo-dynamic status. Transoesophageal echocardiographyshould be widely performed to better analyse thelesions, especially in cases with inconclusive TTE.

2. Perivalvular extension/infectiousindicationsThese represent the second most frequent indication for earlysurgery in Europe.4 In the European guidelines, the infectious

Figure 5 Severe native valve IE with commissural abscess and perforation. (A) Vegetation and pseudoaneurysm (thick arrow) of the poster-ointernal commissure of the mitral valve, associated with a small vegetation (thin arrow). (B) Fistulization of the pseudoaneurysm into the leftatrium causing massive mitral regurgitation (arrow). (C) Three-dimensional echocardiography showing the commissural abscess (arrow). (D)Anatomical correlation: surgical specimen showing the commissural abscess (arrow). LA, left atrium; LV, left ventricle; AML, anterior mitralleaflet; PML, posterior mitral leaflet.

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complications needing surgery include locally uncontrolled infection,persistent fever, and infection caused by fungi or multiresistant organ-isms.10 Echocardiography plays a key role in the assessment of peri-valvular lesions, including abscess, pseudoaneurysm, and fistula.

Echocardiographic presentation of perivalvular lesions isdescribed in Chapter 1. Abscess formation in aortic IE is adynamic process starting with aortic root wall thickening.30

When a slight thickening of the aortic root is visualized, the diag-nosis of abscess should be suspected and echocardiographyrepeated. The diagnosis is confirmed when the lesion progresses,leading to the formation of an abscess or a pseudoaneurysm(Figure 8). Extensive tissue destruction may also result in the for-mation of fistulae.31– 33 Perivalvular extension may also be

discovered on systematic TEE. Finally, TEE allows an accurateassessment of the site and dimensions of abscesses or pseudoa-neurysms.22 Transthoracic echocardiography and TEE combinedwith pulsed, continuous, and colour Doppler are the techniquesof choice for the diagnosis and localization of fistulae and thequantification of the resulting intra-cardiac shunts. Computed tom-ography (CT) scan has been shown to give useful complementaryinformation for the assessment of the perivalvular extent ofabscesses and pseudoaneurysms.10

Unless severe comorbidities are present, surgery must be per-formed on an urgent basis when a perivalvular complication is diag-nosed by echocardiography.10 However, in a minority of patientscharacterized by rapid and favourable response to antibacterial

Figure 6 Perforation of the anterior mitral leaflet (arrow). (A) TEE. (B) Colour Doppler. (C) Three-dimensional echocardiography. LA, leftatrium; LV, left ventricle; AML, anterior mitral leaflet; PML, posterior mitral leaflet; Ao, aorta.

Figure 7 Perforation and aneurysm of the anterior mitral leaflet (arrows). (A) TEE showing the saccular bulging of the anterior mitral leaflet.(B) and (C ) Anatomical correlation. Visualization of the atrial (B) and ventricular (C) aspect of the mitral aneurysm. LA, left atrium; LV, leftventricle; Ao, aorta.

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therapy with small and stable abscesses, a conservative treatment maybe discussed.22,34,35 A conservative approach might be an option forpatients with non-Staphylococcal IE without heart failure, heart block,severe valvular regurgitation, or dehiscence.10,22,34 Close clinical andbiological monitoring and serial TEE are mandatory in this rare situ-ation.34 Conversely, emergency surgery may be necessary becauseof extensive perivalvular lesions associated with severe heart failure.

Vegetations with increasing dimension on serial TEE examin-ations in a patient with adapted antibacterial therapy are a signof uncontrolled infection and represent another indication forsurgery.10 Transoesophageal echocardiography is the method ofchoice for measuring the size of the vegetation and for follow-up.1

Key pointsPrompt TTE and TEE in IE are required in cases of uncon-trolled infection and in patients at risk for perivalvularextension. Transoesophageal echocardiography is thetechnique of choice for the diagnosis of perivalvular exten-sion and its resulting complications.

3. Embolic events/embolic indicationsVegetations or fragments of vegetation may embolize via the vas-cular bed, resulting in embolic events. This is a common compli-cation of IE occurring in 20–50% of patients10,36 – 40 and carries ahigh risk of morbidity and mortality.10 The most frequent sites ofembolism in left-sided IE are the brain and spleen while pulmonaryembolism is frequent in native right-sided and PM lead IE. Embolicevents may be totally silent in about 20% of IE patients, especiallythose affecting the splenic or cerebral circulation,37 and must bediagnosed by systematic non-invasive imaging.

Embolism may occur before diagnosis as well as after diagnosisduring antibacterial therapy, while it is rare after the completion ofantibacterial therapy. Since echocardiography is the procedure ofchoice for the diagnosis of vegetations (Section 1), TTE and par-ticularly TEE should be performed in case of occurrence of anyembolic event. Echocardiography assesses the number, size,shape, location, echogenicity, and mobility of vegetations.37,40 – 44

Echocardiography is useful for predicting embolic risk and there-fore plays a key role in identifying a subgroup of patients whomight benefit from early surgery to avoid embolism.40– 46 Indeed,some echocardiography characteristics of vegetations are associ-ated with an increased embolic risk. The size and mobility of veg-etations are powerful echocardiographic predictors of newembolic events.40 Patients with vegetations greater than 10 mmare at higher risk of embolism (Figure 9). This risk is even higherin patients with very large (.15 mm) and mobile veg-etations.37,40,42 Thus, careful measurement of the maximal veg-etation size at time of diagnosis and during follow-up is stronglyrecommended as part of the risk stratification. Moreover, embo-lism occurs more frequently in patients with vegetations locatedon the mitral valve (in particular on the anterior mitral leaflet)and when increasing or decreasing size of the vegetation isobserved under antibiotic therapy.36,41 – 43 However, the ability ofechocardiography to predict the individual patient risk for embo-lism remains limited.10,22 Actually, echocardiographic findings arenot the sole predictors of the occurrence of an embolic event.

Figure 8 Evolution of an anterior aortic bioprosthetic abscess(TTE). (A) Initial evaluation showing the absence of abscess for-mation. (B) Second evaluation showing the presence of a newanterior free space corresponding to an abscess. (C) ColourDoppler showing that the abscess communicates with the leftventricle (arrow) (pseudoaneurysm). AO, aorta; LV, left ventricle;LA, left atrium; RV, right ventricle.

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Other factors (i.e. biologic factors, specific microorganisms) play asignificant role.10,37 Importantly, the risk of new embolism ishighest during the first days after the initiation of antibacterialtherapy and the rate of new embolic events drops dramaticallyafter the first 2 weeks of antimicrobial therapy, although somerisk persists when vegetations remain present.38,41,45 For thisreason, the benefits of surgery to prevent embolism are greatestduring the first week of antibiotic therapy.10

The Task Force on the Prevention, Diagnosis, and Treatment ofInfective Endocarditis of the European Society of Cardiology10 rec-ommends surgery to be performed when a large vegetation(.10 mm) is present following one or more embolic episodes.In addition, when associated with known other predictors of acomplicated course (heart failure, persistent infection undertherapy, abscess, and prosthetic endocarditis), the presence of alarge vegetation (.10 mm) indicates an earlier surgical decision.Finally, the decision to operate early in isolated very large veg-etation (.15 mm) is more difficult and must be specific for theindividual patient. Surgery may be preferred when a valve repairseems possible, particularly in mitral valve IE. Finally, as far as pre-vention of embolism is concerned, surgery, when considered, mustbe performed on an urgent basis.

Key pointsEmbolism is a common and severe complication of IE, com-plicating 20–50% of cases of IE. The risk of embolism ishighest during the first 2 weeks of antibiotic therapy and isclearly related to the size, location, and mobility of the veg-etation. The highest risk is observed for large (>10–15 mm)and very mobile vegetations. Echocardiography, particularlyTEE, is the key examination for the diagnosis and descriptionof characteristics of vegetations. The decision to operateearly to prevent embolism depends on several factors,including size and mobility of the vegetation, previous embo-lism, type of microorganism, and duration of antibiotictherapy. The occurrence of embolic events requires sys-tematic TTE and TEE examination.

4. Other complicationsPericarditis: Purulent pericarditis is rare. Infection involving themitral or tricuspid annulus may extend to the pericardium. Puru-lent pericarditis may also be secondary to a pseudoaneurysm of

the proximal aorta, a myocardial abscess, a myocarditis, or aseptic coronary-embolus. Rarely, ruptured pseudoaneurysms orfistulae may communicate with the pericardium, with dramaticand often fatal consequences. Echocardiography is the best exam-ination to diagnose and appreciate the haemodynamic tolerance ofpericarditis and may guide drainage.

Coronary obstruction: In the rare cases of coronary obstructiondue to vegetation embolism, coronary compression, or ostialocclusion by large vegetation, echocardiography may visualize anew left ventricular segmental wall motion abnormality.

Myocarditis: Myocarditis is an uncommon complication of IE, gen-erally associated with abscess formation. Transthoracic echocar-diography plays a key role for the evaluation of global andregional left and right ventricular function in this situation.

Key pointsIn summary, HF, perivalvular infection, and high embolic riskare the three main indications for early surgery. Echocardio-graphy plays a major role in decision-making in IE when oneof these three situations occurs. The presence of HF, abscess,or high embolic risk usually indicates urgent surgery.

Chapter 3: Echocardiography forthe follow-up and prognosticassessment of IEDespite diagnostic and therapeutic advances, mortality is still highin IE. Overall mortality for left-sided IE is 20–25%.47 It is lower forright-sided IE in intravenous drug abusers (IVDA; 4–10%.48,49

Echocardiography (TTE and TEE) is an invaluable adjunct to clinicaldecision-making concerning potential surgical intervention andprediction of short- and long-term prognosis. The role of echocar-diography in this setting can be separated into three different evol-ving periods of the disease: at admission to the hospital, duringhospitalization, and after discharge.

1. Prognostic assessment at admissionPrognosis in IE is influenced by four main factors: the patient’s clini-cal characteristics, the presence or absence of cardiac and non-cardiac complications, the type of infecting microorganism, andthe echocardiographic findings. Patients with heart failure,

Figure 9 Transoesophageal echocardiography showing a large and mobile vegetation (arrows) on a bioprosthetic mitral valve moving fromthe left atrium (A and B) to the left ventricle (C) through the prosthesis. LA, left atrium; LV, left ventricle; RA, right atrium.

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perivalvular complications, and/or Staphylococcus aureus infectionare at highest risk of death and need for surgery in the activephase of the disease.50 Several echocardiographic features havebeen associated with a worse prognosis, including perivalvularcomplications, severe native or prosthetic valve regurgitation orobstruction, low left ventricular ejection fraction, pulmonaryhypertension, large vegetations, and premature mitral valveclosure or other signs of elevated diastolic pressures.

Thus, echocardiography plays an essential role both in diagnosticand prognostic assessment of patients with IE. In addition, echocar-diography is also useful to predict the risk of new embolism.40,41

2. Echocardiographic follow-upunder therapyEchocardiography must be used for follow-up of patients with IEunder antibiotic therapy, along with clinical follow-up. Thenumber, type, and timing of repeat examinations depend on theclinical presentation, the type of microorganism, and the initialechographic findings. Weekly TTE may be sufficient in non-complicated streptococcal native IE, while more frequent TEEand TTE controls can be necessary in postoperative staphylococcalearly PVE. During hospitalization, serial echographic studies mayshow a gradual reduction in size, decrease in mobility, and increasein echogenicity of vegetations. However, these lesions may eitherdisappear or remain unchanged long after the acute phase of thedisease, even after healing of the disease. In one study, failure todecrease vegetation size with antibiotic treatment was associatedwith an increased risk of embolism.36 Conversely, Vilacostaet al.41 showed that most vegetations (83.8%) remains constantin size under therapy, and that this does not worsen prognosis.However, in this study, both increase of vegetation size under anti-biotic therapy (observed in 10.5% of patients with IE) andreduction of vegetation size under therapy were associated withan increased embolic risk. Thus, increasing vegetation size undertherapy must be considered as a risk factor for new embolicevent, while unchanged or reduced vegetation size undertherapy may be more difficult to interpret.10

3. Follow-up after discharge andlong-term prognosisAfter hospital discharge, the main complications include recur-rence of infection, HF, need for valve surgery, and death. Emboli-zation is rare. The 6-month mortality rate in IE is between 22and 27%.3,51– 53 The risk of recurrence is low (1.3–6.6% in tworecent series54,55) but is higher in patients with PVE, perivalvularextension, and IVDA. Similarly, the risk of HF and need for latesurgery is low after discharge, but is higher in patients with perian-nular extension and persisting valve regurgitation.

For these reasons, both clinical and echocardiographic follow-upare recommended after discharge. To monitor the development ofsecondary HF, the recent ESC guidelines10 recommend performingan initial baseline TTE at the completion of antimicrobial therapy,and serial examinations at 1, 3, 6, and 12 months during the firstyear following completion of therapy. Repeat TEE is usually notnecessary after discharge, except in selected patients with incom-plete surgical treatment or persistent valve or prosthetic

dysfunction. After discharge, recommendations for surgery arethose of conventional valvular guidelines.

Key pointsIn association with clinical and microbiological parameters,echocardiography is helpful for rapid prognostic assessmentat admission and should be used to choose the best thera-peutic option. Transthoracic echocardiography and/or TEEare useful for follow-up of patients with IE under therapy.

Recommendations10

(1) Repeat TTE and TEE are recommended as soon as anew complication of IE is suspected and should be con-sidered during follow-up of uncomplicated IE, in orderto detect new silent complications and monitor veg-etation size.

(2) TTE is recommended before discharge for subsequentcomparison.

(3) Clinical and echocardiographic periodic follow-up ismandatory during the first year after the end of anti-biotic treatment.

Chapter 4: IntraoperativeechocardiographyAlthough few data in IE patients are available on the impact of sys-tematic use of intraoperative TEE,56 the Task Force on the Preven-tion, Diagnosis, and Treatment of Infective Endocarditis of theEuropean Society of Cardiology recommends intraoperative TEEto be performed in all cases of IE requiring surgery.10 In fact,intraoperative TEE in this setting may provide additional diagnosticinformation before bypass, is able to assess the adequacy of thesurgical procedure before the chest is closed, and therefore maymodify the operative plan.

In IE, meticulous echocardiographic evaluation, generally includ-ing TEE, is systematically performed to select patients referred forsurgery. Nevertheless, infective lesions may progress since the lastpreoperative examination. Vegetations may grow or embolize.56

The infectious process may rapidly extend to form or worsenabscess and/or fistulous tracts or to involve other valves. Thus, apre-pump TEE in the operative room allows a final evaluation ofvalvular and perivalvular lesions. This exam may provide newdata on the extent of the infectious process and valve reparability,and therefore confirm or modify the operative plan. In a recentseries, systematic pre-pump intraoperative TEE changed theinitial operative plan in 11% of cases.56 Pre-pump TEE is particu-larly helpful to determine the best surgical approach by identifyingthe mechanism of regurgitation (i.e. valve repair or valve replace-ment) and the extension of the lesions outside the valvetissue.56– 58

Post-pump intraoperative TEE is fundamental in the evaluationof the immediate surgical result in patients with infected andfriable tissues, especially to assess the result of valve repair(highly sensitive to detect a significant residual regurgitation),valve replacement (analysis of prosthesis function, detection, local-ization, and quantification of perivalvular leaks), and complex

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perivalvular repair.56,58 Immediate reoperation may be undertakenbased on TEE findings, in a percentage of cases reaching 10% whenusing systematic intraoperative TEE.56 Yet, the role of the surgeonto ascertain macroscopic eradication of all infected tissue remainsfundamental because intraoperative TEE is not sensitive enough toidentify all foci of residual infection. Post-pump intraoperative TEEalso serves as a reference document of the surgical result for sub-sequent post-operative echocardiography. In addition, a post-pump intraoperative TEE also helps in the assessment and treat-ment of difficult weaning from the cardiopulmonary bypasspump and can guide difficult de-airing.56

Key pointsIntraoperative TEE in IE may provide useful data for theplanning of surgery, is essential for the immediate qualitycontrol of the operative procedures, has the potential toimprove surgical results, and is a reference for futurestudies. A wide experience and a high degree of expertiseare required to perform this examination that guides thesurgeon and may change the course of operation. Theimpact of intraoperative TEE leads to recommend itsroutine and systematic use, especially in cases of conserva-tive valve surgery and other complex procedures.

Recommendation:Intraoperative TEE is recommended in all patients with IEundergoing cardiac surgery.

Chapter 5: Echocardiography inspecific clinical conditions

1. Prosthetic valve infective endocarditisIncidence and pathophysiologyProsthetic valve endocarditis is the most severe form of IE andoccurs in 1–6% of patients with valve prostheses,59 –64 accounting

for 10–30% of all cases of IE60 with similar incidences observed inmechanical and bioprosthetic valves.

The pathophysiology of PVE differs from that of native valveendocarditis (NVE) in several aspects. Prosthetic valve endocarditisis characterized by a lower incidence of vegetations and higher inci-dence of abscesses and perivalvular complications.60 The anatom-ical involvement differs between PVE affecting mechanical vs.bioprosthetic valves.61 In mechanical valves, the infection usuallyinvolves the junction between the sewing ring and the annulus,leading to perivalvular abscess, dehiscence, pseudoaneurysms,and fistula. In bioprosthetic IE, infection is more frequentlylocated on the leaflets, leading to cusp rupture, perforation, andvegetations.

The usual consequence of PVE is new prosthetic regurgitationcausing heart failure. Less frequently, large vegetations may causeprosthetic valve obstruction.

Echocardiographic findingsAlthough fluoroscopy is valuable in the setting of PVE, echocardio-graphy, particularly TEE, plays the key role in the diagnosis andevaluation of these patients. Both the anatomical lesions andtheir haemodynamic consequences can be completely evaluatedby Doppler echocardiographic techniques. Transoesophagealechocardiography is mandatory in PVE because of its better sensi-tivity and specificity for the detection of vegetations, abscesses, andperivalvular lesions in this setting.65

However, the value of both TTE and TEE is lower in PVE than inNVE for several reasons. First, the presence of intracardiacmaterial may hinder the identification of both vegetations andabscesses, explaining the lower sensitivity of TEE in PVE whencompared with NVE. Consequently, a negative echocardiogramis relatively frequently observed in PVE,17 and does not rule outthe diagnosis of IE. Repeat examination must be performed if clini-cal level of suspicion is still high (Figure 10).17 Secondly, it may bedifficult to differentiate between thrombus or strand and a veg-etation (Figure 11) and between bioprosthetic degeneration and

Figure 10 Evolution of a mitral bioprosthetic valve endocarditis. Left panel: initial evaluation showing an apparently normal bioprosthesis.Right panel: second evaluation performed because of persistent fever, showing the presence of a new periprosthetic mitral regurgitation(arrow). LV, left ventricle; LA, left atrium; RV, right ventricle.

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infective lesions. Thirdly, the diagnosis of an abscess is frequentlymore difficult in PVE, particularly in the early postoperativeperiod after valve replacement. For example, a thickening of theaortic root is frequently observed after a Bentall procedure,mimicking abscess formation despite the absence of IE. Finally, anew dehiscence of a prosthetic valve represents the third maindiagnostic criterion for IE.11 Infective endocarditis must be sus-pected in the presence of a new periprosthetic regurgitation,even in the absence of a vegetation or abscess. Transoesophagealechocardiography has a better sensitivity than TTE for this diagno-sis, especially in mitral PVE. However, the diagnostic value of aprosthetic regurgitation depends on knowing of a previousnormal TEE examination. For this reason, systematic postoperativeechocardiography must be performed after any valve replacementin order to serve as reference for better interpretation of futureechocardiographic abnormalities. As a consequence of these limit-ations, the Duke criteria have a lower sensitivity for the diagnosisof PVE, when compared with native valve IE.66,67

Role of echocardiography during treatment and follow-upof prosthetic valve endocarditisAs in NVE, echocardiography plays a key role in the prognosticassessment of PVE. The presence of severe prosthetic regurgita-tion or obstruction (Figure 11), periprosthetic complications, andlarge vegetations (Figure 9) are associated with poor outcome inPVE and indicates the need for surgery in the majority of patients,unless comorbidities are too severe. In these patients with fre-quently severely destructive lesions, intraoperative echocardiogra-phy is mandatory, particularly in cases of homograft surgery. Innon-complicated PVE treated medically, repeat echocardiographicexaminations are necessary, in order to detect progressive pros-thetic dysfunction.

Key pointsProsthetic valve endocarditis represents one of the mostfrequent and severe form of IE. Both TTE and TEE aremandatory in suspected or definite PVE. Perivalvular

complications are most frequent in aortic PVE, and arebetter assessed by TEE. However, the sensitivity andspecificity of both TTE and TEE are lower in PVE thanin NVE. Echocardiography is also recommended for theperoperative and postoperative assessment of operatedpatients and for the follow-up of patients treated bymedical therapy alone, because of the risk of late prosthe-tic dysfunction.

2. Cardiac device-related infectiveendocarditisInfections of cardiac devices, including permanent PMs and implan-table cardioverter defibrillators (ICDs), are associated with sub-stantial morbidity, mortality, and financial cost. Echocardiographyhas a key role in the diagnosis and assessment of patients withthis condition.

Incidence and pathogenesisThe reported incidence of infection of these devices varies widelyamong studies. A recent population-based study found an inci-dence of 1.9 per 1000 device-years.68 The probability of infectionis higher after ICD implantation when compared with a PM implan-tation.68,69 Local device infection has to be distinguished fromcardiac device-related infective endocarditis (CDRIE); the formeris defined as an infection limited to the pocket of the device andshould clinically be suspected in the presence of local signs ofinflammation at the generator pocket. On the contrary, CDRIErefers to an infection extending to the electrode leads, valvularapparatus, or endocardial surface. However, differentiating bothentities is not always possible.69,70 The main pathogenetic mechan-ism of CDRIE is contamination by local bacteriological flora at thetime of device implantation, replacement, or any other sort ofmanipulation.71

Echocardiographic findingsEchocardiography plays a key role in CDRIE and is the technique ofchoice for the detection and sizing of vegetations. Vegetations may

Figure 11 Mitral prosthetic valve endocarditis with prosthetic obstruction (transoesophageal echocardiography). (A) Large vegetation pro-lapsing into the mitral mechanical prosthetic valve (arrow). (B) Central regurgitation associated with the absence of the physiological regurgitantjets (arrow). LV, left ventricle; LA, left atrium; RV, right ventricle.

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be attached to the electrode lead, the tricuspid leaflets, and to theendocardial wall. In addition, this technique will be useful in theevaluation of tricuspid regurgitation, assessment of right heartchamber dilatation, and quantitation of pulmonary artery pressure.Since vegetations can be found anywhere from the superior venacava to the right ventricle, echocardiography should evaluate thewhole infectious lead course. In addition, assessment of theother heart valves, native and prosthetic, is important. In mostpatients, vegetations attached to the electrode lead present witha typical motion and morphology (Figure 12A), and are a major cri-terion for IE. In other cases, lead vegetations may have a sleeve-likeappearance72 and are difficult to distinguish from thrombi(Figure 12B). In this situation, the clinical scenario and a new echo-cardiogram may help the diagnosis. Transthoracic echocardiogra-phy has a poor sensitivity and negative predictive value for thedetection of cardiac device vegetations. Transoesophageal echo-cardiography has a higher sensitivity and specificity than TTE,73,74

but both modalities must be performed for a complete evaluationof patients’ condition.

Difficulties in the detection of lead vegetations by TTE areexplained by the following reasons: presence of reverberationlead echoes, especially in patients with more than one intracardiaclead, atypical location of vegetations (within the superior vena cavaor in the right atrium), and inadequate transthoracic acousticwindow of these usually older patients.73,74 Transthoracic echocar-diography and TEE may be falsely negative. Therefore, a normalechographic examination does not rule out CDRIE. When clinicalsuspicion of CDRIE is high and results from TEE are negative, arepeat TEE is warranted within 7 days.

The Duke criteria are difficult to apply in these patients becauseof lower sensitivity. Modifications of these criteria have been pro-posed, to include local signs of infection and pulmonary embolismas major criteria.72,75 Lung CT and lung scintigraphy may be usedto assess the presence of pulmonary embolism. Septic pulmonaryembolism before extraction of the infected material is common,but its clinical impact is usually low.72,75 The risk of pulmonaryembolism is related to the size of vegetation.

Preliminary experience with intracardiac echocardiography hasbeen reported.76

ManagementCardiac-device related infective endocarditis must be treated withprolonged antibiotic therapy as well as device removal.69 Resultsof echocardiographic examination have been reported to influencethe mode of device removal, some authors recommending surgeryto be performed in patients with very large vegetations.70,77

However, in most cases, device extraction may be performed per-cutaneously without need for surgery, even in cases of large veg-etations, since overall risks are even higher with surgicalextraction.69 Surgery may only be considered with very large veg-etations (.25 mm). Echocardiography (TTE and/or TEE) shouldbe repeated after device extraction, and the existence of residualvegetations and tricuspid valve lesions ruled out. Careful examin-ation of the right ventricle, tricuspid valve, right atrium, and distalsuperior vena cava is essential.73,74

Key pointsAlthough TEE is superior to TTE, both are mandatory insuspected or definite CDRIE, but their sensitivity andspecificity are lower than in native IE. Echocardiographyis also useful for the measurement of vegetation size andshould be repeated after device extraction.

3. Right heart infective endocarditisIncidence and pathophysiologyIn the general population of patients affected by IE, the incidence ofright-sided structure involvement is very low (,5%).78,79

However, in patients with IVDA, the incidence of right-sided IEbecomes preeminent and the most frequently affected valve isthe tricuspid valve (58–80%).80– 82

Echocardiographic methods and findingsThe relative proximity of the tricuspid valve to the ultrasoundtransducer and the young age (and consequent good thoracic

Figure 12 Pacemaker lead infective endocarditis (transoesophageal echocardiography). (A) Typical vegetation on a pacemaker lead (arrow).(B) Thickening of the pacemaker lead with a sleeve-like appearance (arrow). RA, right atrium; LA, left atrium; SVC, superior vena cava.

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ultrasound windows) of many patients at risk for right-sided IEexplain why this valve is often well imaged by TTE. Usually, theright ventricular inflow view and the subcostal views provideuseful information. Careful selection of transducers (sometimeshigher frequency transducers may be used to improve spatial res-olution), the use of the ‘zoom function’, and paying attention to theadjustment of sector width, depth, and focus settings will help inaccurate identification of vegetations.

The need for routine TEE in right-sided IE has been ques-tioned.83 However, TEE may be useful in detecting perivalvularabscess and unusual localizations of right-sided IE such as infectionon the Eustachian valve84,85 or on the Chiari network. Transoeso-phageal echocardiography is also indicated in patients with poorimage quality with TTE, in those who have negative TTE despitea moderate or high level of clinical suspicion of IE (especially inthe setting of staphylococcal bacteraemia),86 and when an associ-ated left heart involvement is suspected. Vegetations on PMleads,73 indwelling catheters, and right-sided prostheses are par-ticularly difficult to diagnose with TTE because reverberationsand artefacts produced by the intracardiac material may masksmall vegetations attached to these structures. When there is asuspicion of right-sided IE in such patients, TEE is usually indicated.

The key echocardiographic finding in right-sided IE is a veg-etation on the tricuspid or rarely the pulmonary valve(Figure 13). Similar to vegetations on the left-sided valves, theytend to be localized on the atrial side of the tricuspid valve andthe ventricular side of the pulmonary valve in the path of the regur-gitant jet. Tricuspid vegetations are often large and may exceed

2 cm (Figure 13, left upper panel). On rare occasions, vegetationsmay be sufficiently large to mimic an intracardiac tumour(Figure 13, right upper panel). Large vegetations (.2 cm) havebeen identified as an independent predictor of mortality togetherwith fungal aetiology.78,87

Entrapment of an embolized vegetation in the tricuspid chordalapparatus is sometimes seen, as well as mural vegetations inpatients with congenital heart diseases and left-to-right shunts(Figure 13, lower panel). Similarly, embolized vegetations havebeen seen floating free in the right ventricle or pulmonary arteryand pulmonary embolism in the setting of high-grade fever maybe the first clinical sign of right-sided endocarditis.88

Limitations and pitfalls in the diagnosis of right-sidedinfective endocarditisOccasionally, the presence of normal anatomical variants such asChiari network or prominent Eustachian valve may causediagnostic confusion, more particularly with TTE. Similarly,venous catheters erroneously placed in the right atrium need tobe identified and distinguished from vegetations. Right atrial throm-bus may be distinguished from vegetation in that it is less likely tolie in the path of the jet and tends to layer on the right atrial wall.Past infection with damage to the tricuspid valve is commonly seenin this group, so the presence of vegetation does not in itself signifythe presence of active infection. Extensive valve destructionand severe regurgitation are a common sequel of right-sidedIE. Although older or healed vegetations tend to be moreechogenic and may even be calcified, this finding cannot reliably

Figure 13 Cases of right-sided infective endocarditis (see text for details). AO, aorta; LV, left ventricle; LA, left atrium; RV, right ventricle;Veg, vegetation; PMW, pacemaker wire; IVSD, interventricular septal defect; TrV, tricuspid valve.

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distinguish new from old infection. It should be underlined thatechocardiographic findings always need to be taken in their clinicalcontext.

Key pointsTransthoracic echocardiography is of major value in theassessment of patients with right-sided IE.

Recommendations10

1. Transoesophageal echocardiography is not mandatoryin isolated right-sided native valve IE with good-qualityTTE examination and unequivocal echocardiographicfindings.

2. The size of the tricuspid vegetation and the severity ofthe tricuspid regurgitation must be evaluated by echo-cardiography, because these measurements have thepotential to influence the therapeutic strategy.

4. Negative blood culture infectiveendocarditisHigher morbidity and mortality have been traditionally attributedto patients suffering endocarditis with negative blood cultures(NBCE).11,22,89 It has been proposed that delay in diagnosis andinitiation of treatment while waiting to obtain positive results inblood cultures would be one of the most important reasons forthis, especially before the advent of echocardiography.11

Incidence of NBCE varies from 5 to more than 10% in mostrecent series.90 The most common reason for obtaining negativeblood cultures in IE is the administration of antibiotics prior tothe collection of samples91 and non-bacterial organisms or fasti-dious slow-growing bacteria.

The routine use of echocardiography has overcome the poten-tial limitations of delay in diagnosis with a clear impact in the prog-nosis of NBCE. Routine echocardiography allows an early diagnosisand oriented treatment approach and therefore overcomes in partthe worse natural history of NBCE patients.92,93 The use of bothTTE and TEE should be recommended in this setting.

Conclusion and future directionsEchocardiography plays a key role in IE, concerning its diagnosis,the diagnosis of its complications, its follow-up under therapy,and its prognostic assessment. Echocardiography is particularlyuseful for the initial assessment of embolic risk and in decision-making in IE. Transoesophageal echocardiography plays a majorrole both before surgery and during surgery (intraoperative echo-cardiography). Echocardiographic results must be taken into con-sideration for both the decision to operate patients or not andthe choice of the optimal timing for surgery. Recent advances inthree-dimensional imaging offer additional importance to the echo-graphic evaluation of patients with IE. In all cases, however, theresults of echocardiographic studies may be interpreted takinginto account the clinical features of the patient.

Conflict of interest: none declared.

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